The applicants will conduct a detailed, prospective examination of tobacco withdrawal symptoms of male and female adolescents who are either heavy users, light users or nonusers of tobacco products (including cigarettes and smokeless tobacco). In adults, physical dependence as documented by the presence of withdrawal symptoms, is known to be an important factor in the maintenance of cigarette smoking, and the intensity of nicotine withdrawal has been shown to be directly correlated to the intensity of nicotine use. It has been suggested that like adults, adolescents may also be physically dependent on nicotine. However, all the studies examining incidence of nicotine withdrawal in adolescents have been retrospective in nature, but they suggest that self-reports from adolescents indicate that they also experience withdrawal during abstinence from nicotine. The specific aims of this proposal are (1) to conduct a prospective and systematic study of nicotine withdrawal symptomatology in adolescents who differ in amount of tobacco use (heavy users, light users, nonusers) using standard nicotine withdrawal measures as well as the Clinical Institute for Narcotic Assessment (CINA) scale-(2) to evaluate gender differences in the incidence of nicotine withdrawal in adolescents, (3) to determine if adolescents experience cognitive performance deficits during nicotine withdrawal and if these deficits are greater in heavy users compared with light users of tobacco products, (4) to evaluate alterations in responsivity to both physical and mental stress during nicotine withdrawal, in heavy and light users of tobacco products, compared with nonusers of tobacco and (5) to document alterations in responsivity of the hypothalamo-pituitary-adrenal (HPA) axis and sympathetic system during nicotine withdrawal and exposure to stress. The results of this study would have substantial implications for the use of nicotine substitution and other treatments in adolescents for the pharmacological management of withdrawal, and could also help elucidate the role of cognitive deficits and stress in maintaining cigarette smoking in adolescents. Determining physical dependence and related changes in adolescent tobacco users may also provide valuable information regarding the process of development and maintenance of nicotine dependence.